Takahiro Yamaguchi

Structure-activity relationships of xanthocillin derivatives as thrombopoietin receptor agonist.

Xanthocillin derivatives, which show thrombopoietin receptor agonist activity, were synthesized through our developed method. Bioassay data suggest the importance of alkene geometry, the presence of substituents at the benzene ring that support hydrophobic character, and the moderate size of the molecule. One of the two isonitrile group of the natural product appears to be dispensable.

Mechanism of resistance and antibacterial susceptibility in extended-spectrum β-lactamase phenotype Klebsiella pneumoniae and Klebsiella oxytoca isolated between 2000 and 2010 in Japan.

Clinical isolates of Klebsiella pneumoniae and Klebsiella oxytoca collected from 20 Japanese medical facilities between 2000 and 2010 were analysed to evaluate the mechanisms of resistance and antibacterial susceptibilities to 14 antimicrobials. Overall, eight of 484 (1.6%) K. pneumoniae and 19 of 359 (5.3%) K. oxytoca were determined to be extended-spectrum β-lactamase (ESBL) phenotype isolates, and the identified ESBLs amongst the K. pneumoniae isolates were CTX-M-2, -3, -14 and -15, and SHV-12. In contrast, overproduction of chromosomal β-lactamase OXY-2, which was due to a distinct mutation at the - 10 promoter region of this gene, conferred the ESBL phenotype to all the K. oxytoca isolates except one. Based on the Clinical and Laboratory Standards Institute breakpoints, all the ESBL phenotype K. pneumoniae were susceptible to doripenem, flomoxef, moxalactam (latamoxef), cefmetazole and tazobactam/piperacillin, whereas the ESBL phenotype K. oxytoca were susceptible to ceftazidime and ceftibuten in addition to the above, with the exception of tazobactam/piperacillin. Amongst the oral antimicrobials, ceftibuten was relatively effective against both ESBL phenotype Klebsiella species compared with levofloxacin and amoxicillin/clavulanic acid.

Efficient combination of multi-user MIMO THP and user selection based on spatial orthogonality

This paper proposes an efficient method for combing multi-user MIMO (MU-MIMO) employing Tomlinson Harashima precoding (THP) with semiorthogonal user selection (SUS). Although the ordering of MU-MIMO THP and SUS create space diversity benefit and multi-user diversity benefit, respectively, a significant computational effort is required, which is expected to be relaxed while retaining the system level performance. The proposed method is inspired by the fact that the ordering calculations of MU-MIMO THP and SUS are commonly based on the spatial orthogonality. If that is the case, the result of the ordering of SUS is fully reused for the ordering of MU-MIMO THP, which can eliminate the calculation process of the ordering of MU-MIMO THP. The effectiveness of the proposed method is demonstrated in comparison with the traditional method with the ordering of MU-MIMO THP by means of computer simulations.

Theoretical Shannon Capacity Performance of Nonlinearly Amplified Uplink OFDMA Signals in the Presence of Terminal Mobility

This paper proposes the theoretical derivation method of the Shannon capacity for nonlinearly amplified uplink Orthogonal Frequency Division Multiple Access (OFDMA) in the presence of terminal mobility. In our theoretical derivation, the impact of the intercarrier interference (ICI) arising from terminal mobility as well as the multiuser interference (MUI) caused by nonlinear amplification of the mobile stations (MSs) on OFDMA signals is taken into account. Considering the fact that these interferences differ with the sub-carrier allocation methods such as localized FDMA (LFDMA) and interleaved FDMA (IFDMA), we derive the probability density function (PDF) of the instantaneous signal-to-noise-plus-distortion-plus-interference ratio (SNDIR) for each sub-carrier allocation method. Since the SNDIR is successfully expressed in the closed form, the proposed formula enables us to evaluate the Shannon capacity without conducting time consuming computer simulations.

Comparison of the risk of acquiring in vitro resistance to doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli

To compare the risk of acquiring in vitro resistance between doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli, the in vitro frequency of resistance was determined. Four strains carrying multiple β-lactamases such as blaOXA-1 or blaCTX-M-27 as well as blaCTX-M-15 and blaTEM-1 were used. No resistant colonies appeared on doripenem-containing plates, whereas resistant colonies were obtained from three of four test strains against tazobactam/piperacillin using agar plate containing 8- to 16-fold MIC of each drug. These three acquired tazobactam/piperacillin-resistant strains were not cross-resistant to doripenem, and they showed 1.9- to 3.1-fold higher piperacillin-hydrolysis activity compared to those of each parent strain. The change of each β-lactamase mRNA expression measured by real-time PCR varied among three resistant strains. One of three tazobactam/piperacillin-resistant strains with less susceptibility to ceftazidime overexpressed both blaCTX-M-15 and blaTEM-1, and the other two strains showed higher mRNA expression of either blaTEM-1 or blaOXA-1. These results demonstrate that multiple β-lactamases carried by CTX-M-15-producing E. coli contributed to the resistance to tazobactam/piperacillin. On the other hand, these resistant strains maintained susceptibility to doripenem. The risk of acquiring in vitro resistance to doripenem by CTX-M-15-producing E. coli seems to be lower than that to tazobactam/piperacillin.